The long-term goals of this project are to elucidate the sequence of cellular and molecular events occurring during skeletal muscle development. The project has two components: (a) describing muscle cell lineage from the earliest mesodermal precursor to the multinucleated muscle fiber; and (b) investigating regulatory mechanisms controlling the transit of myoblastic cells from one recognizable compartment to the next. As a means of identifying cells residing in discrete cell lineage states we have chosen a clonal assay because: (a) it permits us to examine individual cells within a total tissue population which is extremely heterogeneous; and (b) it permits us to obtain viable, clonally restricted, cells whose subsequent ifferentiation can be manipulated in vitro. Methods used involve clonal cell culture of chick, mouse and human muscle, tissue transplantation, measurement of protein and mucopolysaccharide synthesis, enzymology, virology, immunogenetics. BIBLIOGRAPHIC REFERENCES: Hauschka, S. D. (1976) Application of Clonal Assay Methods to the Analysis of Tissue Development and Diseased States. NIH Symposium on Aging. In press. Hoffman, A. S., Ratner, B. D., Horbett, T. A., Weathersby, P. K., Sasaki, T., Hanson, S. R., Harker, L. A., Whiffen, J. D., Hauschka, S. D., Venkataraman, S. (1977) The Blood Compatibility and Unique Biological Interactions of Hydrophilic-Hydrophobic Copolymers. 23rd Annual Meeting, The American Society for Artificial Internal Organs.